Molecules with both anti-cancer and anti-inflammatory properties would constitute a new approach for treating cancer. Inflammation is closely linked to cancer, and the presence of inflammation strongly correlates with the development of pre-cancerous lesions, suggesting that the presence of inflammation can induce or facilitate carcinogenesis. Various biochemical targets may be evaluated. COX-2 is the most frequently evaluated oxygenase for assessing anti-inflammatory/anticancer potential. Other targets such as NF-kB, cytokines, chemokines, fibroblast growth factor (FGF), and VEGF have also been used.
The cytotoxicity of (Z)-2-amino-5-(1-benzyl-1H-indol-3-yl)methylene-1-methyl-1H-imidazol-4(5H)-ones against human tumor cell lines (A, FIG. 1) has been reported. Related N-benzylindole analogs have displayed radiosensitizing activity (B, FIG. 1) in parallel with their cytotoxic properties. A series of structurally related N-benzylindolyl- and N-benzoyl indolylbarbituric acids (C, FIG. 1) have been reported with significant anticancer activity. A series of thiobarbituric acid analogs (D, FIG. 1) have also been described to inhibit hypoxia-inducible factor 1 (HIF-1).
2-Thiobarbituric acids are anticonvulsant, immunotropic, anti-inflammatory, and antineoplastic agents, as well as anti-hypnotic, and anticancer agents. More importantly, two barbituric acid analogs (FIG. 1B) have been described to possess both anticancer and anti-inflammatory properties.